期刊
MODERN PATHOLOGY
卷 28, 期 5, 页码 715-720出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2014.161
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资金
- Intramural NIH HHS [ZIA BC011427, ZID BC011291] Funding Source: Medline
Glomangiopericytoma (sinonasal-type hemangiopericytoma) is a rare mesenchymal neoplasm with myoid phenotype (smooth muscle actin-positive), which distinguishes this tumor from soft tissue hemangiopericytoma/solitary fibrous tumor. Molecular genetic changes underlying the pathogenesis of glomangiopericytoma are not known. In this study, 13 well-characterized glomangiopericytomas were immunohistochemically evaluated for beta-catenin expression. All analyzed tumors showed strong expression and nuclear accumulation of beta-catenin. Following this observation, beta-catenin glycogen serine kinase-3 beta phosphorylation region, encoded by exon 3, was PCR amplified in all cases and evaluated for mutations using Sanger sequencing. Heterozygous mutations were identified in 12 of 13 tumors. All mutations consisted of single-nucleotide substitutions: three in codon 32 (c.94G4C (n = 2) and c.95A4T), four in codon 33 (two each c.98C4G and c.98C4T), two in codon 37 (c.109T4G), one in codon 41 (c.121A4G), and two in codon 45 (c.133T4C). At the protein level, these substitutions would lead to p.D32H, p.D32V, p.S33C, p.S33F, p.S37A, p.T41A, and p.S45L mutations, respectively. Previously, similar mutations have been reported in different types of cancers and shown to trigger activation of beta-catenin signaling. All analyzed glomangiopericytomas showed prominent nuclear expression of cyclin D1, as previously shown for tumors with nuclear expression of beta-catenin as a sign of oncogenic activation. These results demonstrate that mutational activation of b beta-catenin and associated cyclin D1 overexpression may be central events in the pathogenesis of glomangiopericytoma. In additon, nuclear accumulation of beta-catenin is a diagnostic marker for glomangiopericytoma.
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